Pegloticase + Methotrexate for Gout
Recruiting in Palo Alto (17 mi)
+115 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Waitlist Available
Sponsor: Amgen
No Placebo Group
Prior Safety Data
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?The study consists of 24-week double-blind trial to evaluate the non-inferiority of the efficacy and safety of pegloticase Q4W with MTX versus pegloticase Q2W with MTX, followed by a 24-week open-label extension of pegloticase Q4W with MTX, in participants with uncontrolled refractory gout.
The main objective of the study is to evaluate the effect of pegloticase 16 mg administered Q4W with MTX versus pegloticase 8 mg administered Q2W with MTX, on the response rate during Month 6, as measured by the sustained normalization of sUA to \< 6 mg/dL for at least 80% of the time.
Do I have to stop taking my current medications for this trial?You will need to stop taking any oral urate-lowering therapy (ULT) for at least 7 days before starting methotrexate and continue not taking it during the trial. The protocol does not specify other medications, but you should discuss your current medications with the trial team.
Is the drug Pegloticase a promising treatment for gout?Yes, Pegloticase is a promising drug for treating gout, especially when used with methotrexate. This combination significantly improves the response rate, helping more patients benefit from the treatment.15678
What safety data is available for Pegloticase and Methotrexate treatment for gout?Pegloticase, used for chronic refractory gout, has shown efficacy in reducing serum uric acid and improving joint function, but it is associated with a higher risk of adverse events, including infusion-related reactions and gout flares. Combining Pegloticase with Methotrexate may improve response durability by reducing antidrug antibody development. Clinical trials and studies, such as the MIRROR study, are exploring the safety and efficacy of this combination. However, infusion reactions remain a significant concern, and anti-inflammatory strategies may be needed to mitigate these effects.12459
What data supports the idea that Pegloticase + Methotrexate for Gout is an effective drug?The available research shows that combining Pegloticase with Methotrexate improves the effectiveness of the treatment for gout. One study found that adding Methotrexate helps more patients respond to Pegloticase, increasing the response rate from 42% when Pegloticase is used alone. This combination helps prevent the body from developing antibodies that can make Pegloticase less effective. Another study confirmed these findings, showing that the combination is effective in patients with uncontrolled gout. This suggests that Pegloticase with Methotrexate is a more reliable option compared to using Pegloticase by itself.13457
Eligibility Criteria
Adults over 18 with uncontrolled refractory gout, who have high uric acid levels and haven't responded to standard treatments. Participants must stop any oral gout medications before starting the trial and use contraception if necessary. Women of childbearing potential need negative pregnancy tests.Participant Groups
The study is testing whether giving Pegloticase every four weeks with Methotrexate (MTX) is as effective as every two weeks for reducing uric acid in gout patients. The first half is blinded, then all get the four-week treatment for another six months.
2Treatment groups
Experimental Treatment
Group I: Pegloticase + Methotrexate Q4WExperimental Treatment2 Interventions
16 mg pegloticase will be administered intravenously every 4 weeks for 24 weeks during double blind treatment and 24 weeks during open label.
Group II: Pegloticase + Methotrexate Q2WExperimental Treatment2 Interventions
8 mg pegloticase will be administered intravenously every 2 weeks for 24 weeks during double blind treatment and 16 mg pegloticase every 4 weeks for 24 weeks during open label.
Pegloticase is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Krystexxa for:
- Chronic gout in adult patients refractory to conventional therapy
🇪🇺 Approved in European Union as Krystexxa for:
- Disabling tophaceous gout
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Arizona Arthritis and RheumatologyChandler, AZ
New Generation Of Medical ResearchNaples, FL
Arizona Arthritis and Rheumatology ReseFlagstaff, AZ
Arizona Arthritis & RheumatologySun City, AZ
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Who is running the clinical trial?
AmgenLead Sponsor
Horizon Therapeutics Ireland DACLead Sponsor
References
New advances in the treatment of gout: review of pegloticase. [2021]Treatment-failure gout (TFG) affects approximately 50,000 patients or about 1% of the overall population of patients with gout in the United States of America. The severity of TFG is manifested by frequent acute attacks of disabling arthritis, chronic deforming joint disease, destructive masses of urate crystals (tophi), progressive physical disability, and poor health-related quality of life. Pegloticase (Krystexxa(®); Savient Pharmaceuticals, Inc), a novel PEGylated urate oxidase (uricase) enzyme, has been resubmitted for US Food and Drug Administration approval. In a 6-month, placebo-controlled clinical trial, 8 mg of pegloticase for every 2 weeks induced a lytic decrease of serum urate (sUr) concentrations, leading to dissolution of tophi in 40% of patients at final visit. However, 58% were nonresponders to the defined target sUr of 0.36 mmol/L (80% were nonresponders during months 3 and 6), possibly due to anti-body formation. Also, 26%-31% experienced infusion reactions (IRs) and 77% suffered from gout flares. Although long-term data are awaited, an anti-inflammatory strategy, eg, based on glucocorticosteroids, is needed to prevent pegloticase antibody formation leading to IRs and diminished or shortened efficacy, and might also prevent gout flares. According to the current clinical data, pegloticase might have an important role as a (bridging) treatment in sUr-responsive patients for tophi clearance in severe chronic refractory gout.
Infusion-related reactions with pegloticase, a recombinant uricase for the treatment of chronic gout refractory to conventional therapy. [2018]In clinical trials of pegloticase, a PEGylated uricase developed for treatment of gout refractory to conventional therapy, infusion-related reactions (IRs) were the second most frequent adverse event reported.
Pegloticase failure and a possible solution: Immunosuppression to prevent intolerance and inefficacy in patients with gout. [2018]Pegloticase is a highly effective therapy for patients with refractory and/or tophaceous gout, but has a high discontinuation rate (30-50%) due to development of anti-drug antibodies causing loss of efficacy and risk of infusion reactions.
Pegloticase in Combination With Methotrexate in Patients With Uncontrolled Gout: A Multicenter, Open-label Study (MIRROR). [2022]To examine the efficacy and safety of pegloticase in combination with methotrexate (MTX) in patients with uncontrolled gout in an exploratory, open-label clinical trial (ClinicalTrials.gov: NCT03635957) prior to a randomized, controlled trial.
Pretreatment and Coadministration With Methotrexate Improved Durability of Pegloticase Response: An Observational, Proof-of-Concept Case Series. [2023]Pegloticase is used for treatment of refractory gout, which has failed maximal medical management, but only 42% of patients respond completely to treatment because of the presumed development of antidrug antibodies, which rapidly clear the pegloticase molecule. Immunomodulatory medications temper antidrug antibody development in other diseases. The aim of this case series was to investigate the utility of adding methotrexate to a pegloticase regimen to increase the response durability in a real-world practice setting.
The effect of immunomodulators on the efficacy and tolerability of pegloticase: a systematic review. [2021]Pegloticase is a recombinant PEGylated uricase that converts relatively insoluble urate to highly water-soluble allantoin, which is readily excreted by the kidneys. It is the first and only biologic treatment indicated for refractory or uncontrolled gout. Clinical trials showed a 6-month pegloticase responder rate of 42%, with the non-responder rate largely being attributed to the development of high-titer anti-drug antibodies (ADAs) against pegloticase. Immunomodulation attenuates ADA formation to biologics in a number of autoimmune conditions, but their use with pegloticase for uncontrolled gout is less established. This systematic review examined published cases of refractory gout patients treated with immunomodulation in combination with pegloticase.
Effect of Leflunomide on Pegloticase Response Rate in Patients with Uncontrolled Gout: A Retrospective Study. [2022]Pegloticase, a PEGylated uricase for uncontrolled gout, rapidly lowers serum urate (SU). Not all patients complete a full-therapy course because anti-pegloticase antibodies can develop, causing efficacy loss and infusion reactions. The literature and clinical trial data indicate that methotrexate co-administration markedly improves pegloticase response rates from the established monotherapy response rate of 42%. Unfortunately, methotrexate use is restricted by kidney disease, which is often present in uncontrolled gout patients. Leflunomide is less restricted in patients with renal dysfunction. This study examined the treatment response rate of pegloticase co-administered with leflunomide.
A multicentre, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase (MIRROR): 12-month efficacy, safety, immunogenicity, and pharmacokinetic findings during long-term extension of an open-label study. [2022]Publications suggest immunomodulation co-therapy improves responder rates in uncontrolled/refractory gout patients undergoing pegloticase treatment. The MIRROR open-label trial showed a 6-month pegloticase + methotrexate co-therapy responder rate of 79%, compared to an established 42% pegloticase monotherapy responder rate. Longer-term efficacy/safety data are presented here.
Evaluation of the efficacy and safety of pegloticase for the treatment of chronic refractory gout through meta-analysis. [2023]Gout is the most common arthritis that affects more than 2% of adults in developed countries. 3% to 4% of gout is chronic refractory gout. Conventional treatments are considered invalid. A new drug, pegloticase is used to treat chronic refractory gout, and there are still many questions about efficacy and safety. We searched PubMed, web of science, and the Cochrane Library. Preprints and references of related literature were also considered. Related efficacy and safety indicators were statistically analyzed by Review Manager 5.4 to conduct meta-analysis. A total of one article and one clinical trial were included. Pegloticase is able to reduce serum uric acid and reduce tender joints, thereby improving joint function. But pegloticase has more adverse events. Pegloticase can be used to treat chronic refractory gout. However, Pegloticase has a higher risk of adverse events. Considering the efficacy and safety, the scope of clinical applications of pegloticase can be further widened in patients in good medical condition.